22.6 Transfusion Products & Acute Transfusion Reactions

5. Transfusion Medicine: Products, Triggers & Adverse Reactions

Blood Products & Evidence-Based Transfusion Triggers

• Packed Red Blood Cells (PRBC): One standard unit raises adult haemoglobin by approximately 10 g/L.
  • Restrictive Trigger (NICE NG24): Hb <70 g/L with a target post-transfusion level of 70–90 g/L in hemodynamically stable, non-bleeding adult patients.
  • Acute Coronary Syndrome Trigger: Hb <80 g/L with a target post-transfusion level of 80–100 g/L in patients with active myocardial ischaemia or acute coronary syndrome.
• Platelets: One adult therapeutic dose (ATD, pool of 4–6 donor units or single apheresis unit) raises platelet count by 20–40 x 10^9/L.
  • Prophylactic trigger in stable bone marrow failure: <10 x 10^9/L;
  • Lumbar puncture, central venous catheter placement, or minor surgery: <50 x 10^9/L;
  • Major surgery, trauma, or active severe bleeding: <50 x 10^9/L;
  • Neurosurgery or intraocular ophthalmic surgery: <100 x 10^9/L.
• Fresh Frozen Plasma (FFP): Contains all clotting factors and physiological anticoagulants. Indicated for multiple factor deficiencies (severe liver disease, massive transfusion, DIC) with active bleeding or prior to invasive surgery. Standard dose: 12–15 mL/kg. NOT indicated for simple volume expansion or minor non-bleeding coagulopathy.
• Cryoprecipitate: Rich in fibrinogen, Factor VIII, vWF, and Factor XIII. Indicated when fibrinogen is <1.5 g/L in bleeding patients (massive obstetric haemorrhage, trauma, DIC). Standard adult dose: 2 pools (equivalent to 10 donor units).
• Prothrombin Complex Concentrate (PCC, 4-factor): Contains factors II, VII, IX, X, and proteins C and S. Preferred first-line agent for emergency reversal of warfarin in major, life-threatening haemorrhage (co-prescribed with intravenous vitamin K 5–10 mg); vastly superior to FFP due to rapid normalization of INR (<10 minutes) and minimal volume administration.

Acute Transfusion Reactions

                      Acute Dyspnoea During Transfusion
                                      |
        +-----------------------------+-----------------------------+
        |                                                           |
TRALI (Non-Cardiogenic)                                     TACO (Cardiogenic Overload)
- Donor anti-HLA/HNA antibodies                             - Excessive volume / rapid infusion rate
- Capillary leak & neutrophil damage                        - Left ventricular hydrostatic overload
- Normal JVP, Normal BNP                                    - Elevated JVP, Elevated BNP (>1.5x)
- Hypotension / fever                                       - Severe Hypertension
- Bilateral fluffy infiltrates                              - Bilateral infiltrates + cardiomegaly
- Treatment: Oxygen, respiratory support                    - Treatment: Stop, sit up, IV Furosemide

• Acute Haemolytic Transfusion Reaction (AHTR):

  • Cause: ABO incompatibility secondary to clerical identification error. Pre-formed host IgM isohemagglutinins rapidly bind and lyse transfused donor erythrocytes via classical complement activation.
  • Features: Immediate onset (within minutes) of fever, chills, flushing, retrosternal chest pain, severe flank/loin pain, profound hypotension/shock, dark red urine (haemoglobinuria), and acute DIC.
  • Management: STOP TRANSFUSION IMMEDIATELY, maintain IV access with vigorous 0.9% saline fluid resuscitation to maintain renal perfusion, check bedside patient ID, and return blood pack and giving set to the transfusion laboratory alongside fresh blood and urine samples.

• Transfusion-Related Acute Lung Injury (TRALI):

  • Pathophysiology: Two-hit mechanism. First hit: Patient's underlying critical illness (sepsis, surgery) primes pulmonary endothelial cells and sequestered neutrophils. Second hit: Infusion of donor plasma containing anti-HLA class I/II or anti-human neutrophil antigen (anti-HNA) antibodies (classically from multiparous female blood donors). These antibodies bind to and activate recipient primed neutrophils within pulmonary capillaries, releasing elastase and reactive oxygen species that damage alveolar-capillary membranes, causing massive non-cardiogenic pulmonary oedema.
  • Features: Acute dyspnoea, hypoxaemia, fever, hypotension, and bilateral fluffy pulmonary infiltrates developing within 6 hours of transfusion.
  • Hemodynamics: Normal JVP, normal pulmonary capillary wedge pressure, and normal serum BNP.
  • Management: Stop transfusion, supportive respiratory therapy (supplemental oxygen, CPAP/BiPAP, mechanical ventilation); avoid aggressive diuresis (patients are frequently hypotensive and intravascularly depleted).

• Transfusion-Associated Circulatory Overload (TACO):

  • Pathophysiology: Pure cardiogenic hydrostatic pulmonary oedema resulting from rapid transfusion of blood volumes that exceed the patient's myocardial or renal circulatory capacity. Risk factors: Age >70, heart failure, renal impairment, severe chronic anaemia.
  • Features: Acute dyspnoea, orthopnoea, cyanosis, tachycardia, severe hypertension, elevated JVP, bilateral basal crackles, and peripheral oedema developing during or within 6 hours of transfusion.
  • Diagnostic Markers: Marked post-transfusion elevation of serum BNP / NT-proBNP (>1.5x baseline) and cardiomegaly on CXR.
  • Management: Stop transfusion immediately, sit the patient upright, administer high-flow oxygen, and give intravenous furosemide (40–80 mg IV). Prevented by transfusing single units slowly (over 3–4 hours) and pre-transfusion oral furosemide in high-risk patients.

• Febrile Non-Haemolytic Transfusion Reaction (FNHTR):

  • Most common reaction; caused by recipient antibodies reacting against donor leukocytes or accumulated pyrogenic cytokines (IL-1, IL-6, TNF-a) released during storage.
  • Features: Isolated, benign temperature rise (>=1°C or >38°C) with rigors and chills, without hypotension, respiratory distress, or pain.
  • Management: Pause transfusion, administer oral paracetamol, exclude ABO mismatch and bacterial sepsis. Transfusion can be restarted at a slower rate once symptoms settle. Universal pre-storage leukodepletion has dramatically reduced incidence.

6. Comparative Table: Differential Diagnosis of Acute Transfusion Reactions